- BioRxiv Biochemistry
- BioRxiv Bioinformatics
- BioRxiv Biophysics
- BioRxiv Cancer Biology
- BioRxiv Pharmacology and Toxicology
- BioRxiv Systems Biology
- BioRxiv Zoology
- by Medina Tretmanis, J., Avila-Arcos, M. C., Jay, F., Huerta-Sanchez, E.Motivation: Local Ancestry Inference (LAI) allows us to study evolutionary processes in admixed populations, uncover ancestry-specific disease risk factors, and to better understand the demographic history of these populations. Many methods for LAI exist, however, these methods usually focus on cases of intercontinental admixture. In this work, we evaluate both existing and novel methods in challenging scenarios, such as downsampled reference panels, intracontinental admixture, and distant admixture events. Results: We present four novel LAI implementations based on neural network architectures, […]
- by Paylakhi, S., Geurgas, R., Yasko, A., Wedow, R., Tegtmeyer, M.Height and most disease risk are known polygenic traits: characteristics governed by multiple genes at different loci instead of a select few. Though we are beginning to understand how genetic variation impacts cell morphology, whether such an analogous polygenic architecture operates at the cellular level, where morphology integrates cytoskeletal organization, organelle positioning, and metabolic state, has yet to be systematically tested. Here, we demonstrate that cellular morphology behaves as a polygenic trait by integrating multimodal modeling, perturbation profiling, and population […]
- by Patton, T., Buck, E. J., Buechlein, A. B., Davis, B. W., Ehrie, A. J., Enbody, E. D., George, E. M., Kuepper, C., Loveland, J. L., Luna, L. W., Rusch, D. B., Thomas, Q. K., Rosvall, K. A., Lipshutz, S. E.In 'sex-role reversed' species, females are socially polyandrous and compete for multiple mates, whereas males conduct the majority of parental care. To understand the extent to which physiological differences between females and males are shaped by sex roles, we examined sex differences in gene expression in 'sex-role reversed' northern jacanas (Jacana spinosa). Given that females compete for mating opportunities, and males cycle between courtship and parental care, we predicted that transcriptomic profiles would be more similar between females and courting […]
- Contributions of error correction and the spindle assembly checkpoint to mitotic timing and fidelityby Ha, G., Qiu, L., Amir, A., Needleman, D.Chromosome segregation is a tightly-regulated process that normally occurs with high fidelity. Errors in chromosome segregation are associated with aging, cancer, and infertility. Initially erroneously attached chromosomes are corrected over the course of mitosis, with the spindle assembly checkpoint preventing entry into anaphase until this error correction is complete. Despite extensive work on the molecular basis of error correction and the spindle assembly checkpoint, it is still unclear how disruption of these processes contribute to chromosome segregation errors. Here, we […]
- by Honda, T., Cortes, D. B.Stentor is a genus of large ciliates that can be found in ponds, lakes, rivers, and other freshwater sources all over the world. Since their initial discovery in 1744, Stentor strains have been isolated from all populated continents. To date, over 50 individual strains have been identified, yet not a single isolate has come from a marine environment. Over 200 years since the initial description of the Stentor genus, our study entails the first concrete discovery of a fully marine […]
- by Maher, C., Saez, I., Radulescu, A.In complex environments, available information does not uniquely define state, requiring attention learning to identify features relevant for learning and decision-making. As a result, human decisions often reflect reasoning that cannot be directly observed from choice. This dual opacity, at the level of agent and observer, poses a fundamental challenge for understanding naturalistic behavior. We inferred latent attention during learning and decision-making by training recurrent neural networks on synthetic data generated from two classes of attention learning models: feature-based reinforcement […]
- by Monge-Loria, M., Brady, C., Wu, H., Aron, A., Garg, N.Iron is an essential component of cellular biology. Thus, iron's low bioavailability is a key evolutionary pressure guiding microbial dynamics in the marine environment. Among marine bacteria, Microbulbifer is an underexplored and functionally versatile bacterial genus, which is commonly associated with sponges, algae, corals and sediments. Previously, genome analyses have revealed that Microbulbifer spp. can degrade polymers and synthesize natural products. Despite their recognized potential to produce secondary metabolites, siderophores are yet to be identified in Microbulbifer , and their […]
- by Peters, E., Heitmann, J., Morath, N., Roth, M., Buehler, N., Nussbaumer, E., Wang, X., Kredel, R., Maurer, S., Dresler, M., Erlacher, D.Lucid dreaming (LD), during which the dreamer is aware that they are dreaming, is frequently induced in laboratory settings by delivering sensory cues during rapid eye movement (REM) sleep. These cues should be incorporated into ongoing dreams and can trigger reflective awareness. This approach relies on the continuity between waking experiences and dream content. In sleep laboratories, participants often dream of the experimental setting itself (lab dreaming), providing a predictable context in which lucidity may emerge. The present studies leveraged […]
- by Ramos-Leon, F., Altouma, V., Goldberg, P., Ibrahim, A., D'Atri, D., Machinandiarena, F., Verdi, V., Missiakas, D. M., Davis, K. M., Ramamurthi, K. S.During infection, Staphylococcus aureus forms dense multicellular structures, called staphylococcal abscess communities (SACs), that are encased in a capsule made of host fibrin to evade host immune defenses. S. aureus cells divide characteristically along successive orthogonal planes, but the contribution of this division geometry to infection is unclear. Here, we show that disrupting orthogonal cell division by deleting the cell division septum placement factor PcdA impairs SAC formation in vivo and in a three-dimensional in vitro model. Loss of PcdA […]
- by Kisthardt, S. C., Perkins, C. E., Gancz, A. S., Lyons, N. S., Thomas, S. A., Vincent, E. C., Tam, J., Melnyk, R., Rose, E. C., Baker, E., Theriot, C. M.Clostridioides difficile infection (CDI) is a severe antibiotic associated disease and a major cause of morbidity and mortality worldwide. CDI is thought to arise from the loss of protective gut microbes that mediate functions such as secondary bile acid metabolism and nutrient competition, yet the relative contributions of these mechanisms remain unclear. To determine how these processes influence C. difficile growth, virulence, and disease, we performed in vitro and in vivo experiments using two Clostridia strains previously associated with colonization […]
- by Suresh Babu, N., Perdios, C., Hallmets, M., Brown, A. T., Coleman, C., Fennessey, C. M., Allers, C., Mostörm, M. J., Khare, P., Zhang, C., Smith, B. T., Golden, N. A., Myers, A., Doyle-Meyers, L., Blaney, A., Blair, R. V., Saied, A. A., Colman, R., Keele, B. F., Le, A., Palmer, C. S., Mudd, J. C.Nutrient metabolism influences HIV-1 replication, antiviral immunity, and chronic inflammation, yet is difficult to leverage for therapeutic gain. We sought to modulate metabolism in the non-human primate model of HIV-1 by caloric restriction (CR), a modality canonically known for its anti-aging benefits. Four months of 30% CR was safe and resulted in broad and systemic metabolic reprogramming in healthy adult male and female rhesus macaques. Relative to that of ad libitum-fed animals, CR lowered the frequencies of target CCR5+ CD4 […]
- by Xie, E., Schubert, M., Fricke, J., Seligmann, B., Schaks, M., Muesken, M., Steffen, A., Stradal, T. E. B., Haid, S., Rottner, K., Sieben, C.Productive human respiratory syncytial virus (RSV) cell-entry requires coordinated interactions between viral proteins and host-cell factors at the plasma membrane-actin cortex interface. Branched actin networks remodel this interface, but their precise contribution to the early stages of RSV infection remains unclear. Here, we interfered with Arp2/3 complex-dependent actin filament branching by generating A549 cell lines disrupted for expression of the essential Arp2 subunit by CRISPR/Cas9. Permanent loss of Arp2 reduced the infection of the RSV long GFP reporter virus as […]
- by Badji-Churchill, J. E., Birker-Wetger, M., Versteegh, M., Vasquez, R., Komdeur, J.Rapid changes to weather caused by climate change have a negative effect on much of the worlds animal populations and species. Some populations are more vulnerable than others to the effects of climate change, and individuals are particularly vulnerable during early development. Good embryonic development is important for vertebrate species because this can dictate their breeding success and survival rates, and disruptions to this phase can have far reaching fitness effects that can last into adulthood and beyond. We looked […]
- by Subramanian, S., Bolnick, D. I.The predictability of evolution remains a fundamental question in biology. While parallel evolution has been observed across taxa, we lack a mechanistic framework for predicting when evolution will be repeatable versus contingent. Here, we test whether gene network architecture predicts evolutionary repeatability and local (mal)adaptation in natural populations. We sequenced 38 wild Hanseniaspora uvarum yeast strains from two replicated apple varieties across four Connecticut orchards, yielding 29,489 high-quality SNPs. Population genomic analyses suggested that genetic differentiation was structured primarily by […]
- by LI, H., Sierras, A. L., Fan, R., Oeller, M., Schallmoser, K., Hultquist, A., Scheding, S.Myelofibrosis (MF) is the most severe myeloproliferative neoplasm, and current therapies rarely reverse bone marrow fibrosis, highlighting the need for improved disease models and therapeutic targets. Here, we established a humanized MF model by transplanting thrombopoietin (THPO)-overexpressing human bone marrow CD34 cells into humanized bone marrow ossicles generated in immunodeficient NSG mice. THPO overexpression induced progressive reticulin fibrosis in vivo, accompanied by myeloid skewing, increased megakaryocyte clustering, and redistribution of human hematopoietic cells to murine spleen and femur, consistent with […]
- by Garamszegi, L., Nagy, G., Klein, A., Szentivanyi, T., Vasarhelyi, Z., Marko, G., Zsebok, S., Soltesz, Z.Ultra-low volume (ULV) insecticide spraying with deltamethrin as the active ingredient is widely used in mosquito control programs, yet its effectiveness against target mosquitoes and its ecological side effects remain poorly quantified under field conditions in Central Europe. Here, we experimentally evaluated the short-term impact of ground ULV spraying on both mosquito populations and non-target flying insects in Hungary using a paired before-after-control-impact (BACI) design. Mosquitoes were sampled with BG Sentinel traps, while non-target insects were collected using malaise traps. […]
- by Sultana, S., Tawiah, P. O., Jackson, C., Bennis, M., Bhimwal, T., Anane, A., Knoke, L. R., Foti, A., Paz, L., Crompton, M. E., Reichmann, D., Leichert, L. I., Dahl, J.-U.Neutrophils eliminate invading pathogens through the production of reactive oxygen and chlorine species (ROS/RCS), with hypochlorous acid (HOCl) representing the most abundant and bactericidal oxidant produced in this process. Compared to bacterial defenses against ROS, which are well studied, little is known about how pathogens respond to and counter RCS, including HOCl. Here, we identify and mechanistically characterize RcrB, a protein of the uncharacterized DUF417 protein family, for which no role in oxidative stress defense has been described yet. We […]
- by Lv, H., Harrington, W. N., Liu, W., Naser, D., Huan, Y. W., Thames, E., Chopra, P., Pholcharee, T., Seiler, P., Ayala, E., Monterroso, A., Ji, W., Teo, Q. W., Gopal, A. B., Ma, E. X., Wu, D. C., Ardagh, M. R., Mehta, A., Huang, J. J., Tong, M., Honzay, G., Shirkey, B., Guthmiller, J. J., Boons, G.-J., Stadtmueller, B. M., Webby, R. J., Wu, N. C.While influenza A virus undergoes rapid antigenic drift in humans, at least some subtypes, such as H3, have relatively stable antigenicity in natural waterfowl reservoirs, despite the presence of immune pressure. However, the underlying mechanisms remain poorly understood. This study identified and characterized 187 antibodies to H3 hemagglutinin from experimentally infected mallard ducks, 18 of which were further analyzed by cryo-EM. Compared with human H3 antibodies, duck H3 antibodies exhibited higher glycan-binding propensity, more balanced immunodominance hierarchy, and targeted distinct […]
- by Bushnell, B., Bowers, R. M., Villada, J. C.Metagenomic binning and single-cell assembly produce draft genomes whose completeness and contamination vary with experimental and computational choices. Comparing whole bin sets remains difficult because most quality assessment tools report per-bin metrics and operate either with ground truth labels or with inference estimates. GradeBins evaluates complete bin sets under two execution modes while producing matched per-bin and bin-set summaries. For real metagenomes, inference mode integrates bin statistics, mapping depth, taxonomy, and external quality estimates from tools such as CheckM2 and […]
- by Furuhata, Y., Rix, G., Almhjell, P. J., Liu, C. C.Genetic code expansion (GCE) enables the site-specific incorporation of noncanonical amino acids (ncAAs) into proteins but is constrained by reliance on exogenously supplied chiral ncAAs. Achieving intracellular ncAA biosynthesis would enable more scalable and cost-effective GCE. Here, we report the continuous hypermutation and evolution of amino acid synthases that produce high levels of ncAAs inside yeast, thus supporting GCE from simple ncAA precursors. We encoded an engineered 'tyrosine synthase' (TmTyrS) on an error-prone orthogonal DNA replication system (OrthoRep) and selected […]